The therapy of viral pathologies currently uses chemotherapy agents with multiple action mechanisms. In particular, considering flu as a typical viral disease, there are used M2 inhibitors such as Amantadine and neuraminidase inhibitors, such as Oseltamivir and Zanamivir. It is known that the virus are capable of acquiring resistance against antiviral agents, hence there strongly arises the need of therapies alternative to those using antiviral agents, also due to the fact that use of these compounds, especially Amantadine, is often associated to severe adverse effects and thus it is not recommended unless under particular conditions.
In addition, there are several viruses that are not currently covered by efficient antiviral therapies. By way of example, currently there are no therapies capable of fighting Poliovirus. The people intensive migrations that occur nowadays have also spread viral strains typical of some areas of the world to areas where the same were unknown, in other cases they have brought back problems related to viral strains that had been considered eliminated in that specific area. Thus, there strongly arises the need of having efficient therapies and with wide coverage against virus.
Glutathione is present in cells in form of Reduced Glutathione GSH and Oxidized Glutathione GSSG. The GSH:GSSG ratio indicates the antioxidant capacity of the cell. Said ratio is maintained in favour of GSH due to GSSG-r, an enzyme belonging to the class of oxidoreductase, which regenerates GSH starting from GSSG, by transferring electrons transferred from the NADPH cofactor, a derivative of vitamin PP (nicotinic acid). Maintaining a correct GSH:GSSG ratio is an essential requirement for the vitality and wellbeing of the cell. A misbalanced GSH:GSSG ratio was observed in numerous pathologic conditions, for example in viral infections, tumours, cystic fibrosis, neurodegenerative diseases. In said pathologic conditions there arises a misbalance in the GSH:GSSG ratio, which is displaced in favour of GSSG hence the cell loses the oxide-reductive balance thereof.
Administration of GSH was proposed in order to counter such loss of balance. Actually, GSH is the most known and powerful physiological antioxidant, and thus already used as a supplement in anti-aging therapies, and it was surprisingly proven to have antiviral activity (Garaci et al., 1992). The supplementation of GSH however proved to be complex, in that it is poorly absorbed in the gastrointestinal tract. This drawback was overcome by administering GSH precursors, such as S-adenosyl-1-methionine (SAMe) and/or N-acetylcysteine (NAC).
WO/2005/063795 describes the use of GSH derivatives for treating Paramyxovirus, Orthomyxovirus, Herpes Simplex Virus and HIV infections.
WO00/71146 describes the use of GSSG-r in the HIV therapy.
WO/2002/083168 describes a combination of two enzymes: GSSG-r and Glutathione peroxidase (GSH-px) as adjuvants in the therapy with Interferons.
As of date, there has been no indication as regards the therapeutic use of GSSG.